Background: Head and squamous cell carcinoma (HNSCC) in the locally advanced setting is challenging to treat and remains an area of significant morbidity and mortality. For patients who are cisplatin-ineligible and considered unresectable, there is no clear standard of care including the choice of radiosensitizer.
Methods: OVID Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched. Randomized clinical trials (RCTs) of cisplatin-ineligible unresectable HNSCC patients who were randomized to an immune checkpoint inhibitor concurrent with radiation compared to a control arm were included. Data was pooled and assessed using a random-effects model for the meta-analysis.
Results: Three eligible RCTs were identified and analyzed which comprised 594 patients whose median age ranged from 65-72 years. There was no difference in overall survival (pooled HR 1.02, 95% CI 0.76-1.37, p = 0.88) or PFS (pooled HR 0.92, 95% CI 0.68-1.23, p = 0.56). Grade greater than or equal to 3 adverse events were favored to be less in the immunotherapy arm.
Conclusions and relevance: Immune-checkpoint inhibitors are not superior to cetuximab when used with definitive radiation in HNSCC. Further study is warranted, given its potential signal for non-inferior survival with less toxicity profile trends.
Keywords: Immune-checkpoint inhibitors; chemoradiation; cisplatin-ineligible; head and neck squamous cell carcinoma; meta-analysis.
Head and neck squamous cell carcinoma is a challenging cancer to treat. Cisplatin chemotherapy is often the preferred treatment combined with radiation, but alternatives are needed for patients who are not fit for this option.This study reviewed past clinical trials to understand how effective and safe immune checkpoint inhibitors are when combined with radiation therapy for these patients when compared to concurrent cetuximab and RT.Our results showed immune checkpoint inhibitors did not prove to be more effective than cetuximab, but they might offer a less toxic alternative. More research is needed to confirm these findings and explore new treatment options for patients who cannot receive cisplatin in combination with radiation.